1. Field of the Invention
This invention relates generally to nucleic acid sequences encoding polypeptides that are associated with Type 1 diabetes. In particular, this invention relates to nucleic acid and amino acid sequences encoding a member of the small ubiquitin-like modifier (SUMO) gene family, and methods of their use to facilitate the diagnosis of patients suffering from type 1 diabetes.
2. Background Art
Diabetes is a chronic condition that affects an individual's ability to manufacture and utilize the hormone insulin, which is necessary for the conversion of food into energy. Patients suffering from diabetes have an increased risk of developing side effects such as blindness, heart disease, kidney failure, and neurological disease. Type 1 diabetes (T1D) (also known as insulin-dependent diabetes (IDDM) or juvenile onset diabetes) is the more severe form of the illness and is defined by the development of ketoacidosis in the absence of insulin therapy. In patients suffering from Type 1 diabetes, the pancreas produces little or no insulin, and therefore, insulin must be injected daily. Non-insulin-dependent diabetes mellitus (NIDDM or type 2 diabetes) is characterized by persistent hyperglycemia but rarely leads to ketoacidosis. Type 2 diabetes generally manifests after age 40, and therefore, is also known as adult onset-type diabetes. Type 2 diabetes can result from genetic defects that cause both insulin resistance and insulin deficiency.
It is believed that there are mutations in a number of genes that likely contribute to Type 1 diabetes. For example, the insulin-dependent diabetes mellitus 1 locus (IDDM1) on chromosome 6 may harbor at least one susceptibility gene for Type 1 diabetes. It is unknown what effect a mutation at this locus has on a patient's risk, however, this region of chromosome 6 also has genes for antigens that normally tell the immune system not to attack itself. In Type 1 diabetes, the body's immune system mounts an immunological assault on its own insulin and the pancreatic cells that manufacture it.
To date, about 10 loci in the human genome have been found that seem to confer susceptibility to Type 1 diabetes, including: 1) a gene at the locus IDDM2 on chromosome 11, and 2) the gene for glucokinase (GCK), an enzyme that is key to glucose metabolism which helps modulate insulin secretion, located on chromosome 7. Some loci, e.g. IDDM4, IDDM5, and IDDM8, have recently been identified as being correlated with susceptibility to Type 1 diabetes (Twells et al., 2003, 72:231–42; Twells et al., 2001; Nakagawa et al., 1998; Eckenrode et al., 2000; Luo et al., 1995; Luo et al., 1996; Owerbach, 2000; Davies, 1994; Delepine, 1997). In particular, IDDM5 was shown to be linked to a 5-cM genomic interval on chromosome 6q25 (Luo et al., 1995; Luo et al., 1996).
Although it is known in the art that many loci correlate with susceptibility to Type 1 diabetes, it is not known what the susceptibility genes are within most of these intervals. Therefore, what is needed in the art are unique nucleic acid and polypeptide sequences that are associated with Type 1 diabetes. Also needed are methods of facilitating the diagnosis of Type 1 diabetes through the use of such nucleic acid sequences, polypeptide sequences, and unique polymorphisms within these sequences, particularly prior to the clinical onset of the disease.